Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort

Background. Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence. Method. A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy. Results. The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia. Conclusions. Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course

A new method to analyse the pace of child development: Cox regression validated by a bootstrap resampling procedure

<p>Abstract</p> <p>Background</p> <p>Various perinatal factors influencing neuromotor development are known from cross sectional studies. Factors influencing the age at which distinct abilities are acquired are uncertain. We hypothesized that the Cox regression model might identify these factors.</p> <p>Methods</p> <p>Neonates treated at Aachen University Hospital in 2000/2001 were identified retrospectively (n = 796). Outcome data, based on a structured interview, were available from 466 children, as were perinatal data. Factors possibly related to outcome were identified by bootstrap selection and then included into a multivariate Cox regression model. To evaluate if the parental assessment might change with the time elapsed since birth we studied five age cohorts of 163 normally developed children.</p> <p>Results</p> <p>Birth weight, gestational age, congenital cardiac disease and periventricular leukomalacia were related to outcome in the multivariate analysis (p < 0.05). Analysis of the control cohorts revealed that the parents' assessment of the ability of bladder control is modified by the time elapsed since birth.</p> <p>Conclusions</p> <p>Combined application of the bootstrap resampling procedure and multivariate Cox regression analysis effectively identifies perinatal factors influencing the age at which distinct abilities are acquired. These were similar as known from previous cross sectional studies. Retrospective data acquistion may lead to a bias because the parental memories change with time. This recommends applying this statistical approach in larger prospective trials.</p

Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p &#60; 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance

Congenital Cytomegalovirus Mortality in the United States, 1990–2006

Cytomegalovirus (CMV) is a member of the herpes family of viruses, which is transmitted by sexual and non-sexual contact. Human CMV causes a wide variety of infection and illness in healthy adults, in those with compromised immune systems (such as AIDS), in those with cardiovascular disease, and in pregnant women who can pass the infection to their unborn child (congenital CMV). Treatment options for congenital CMV are limited and no effective vaccine to protect against CMV currently exists. Previous studies have demonstrated that African Americans and Mexican Americans are at an increased risk for congenital CMV infections. In this study, the authors examined death certificate data of US Residents from 1990–2006 in which congenital CMV was listed as one of the diagnoses at death. The analysis demonstrated that there is a significant burden of congenital CMV deaths in infants (<1 year old) with African Americans and Native Americans overrepresented. This study helps quantify congenital CMV deaths among US residents and adds further support to the importance of funding CMV vaccine research

Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age – A Follow Up from the PREOBE Cohort

The study was registered at www.ClinicalTrials.gov, identifier:NCT01634464).Background: Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring.Objective: The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life.Design: This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment.Results: At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the offspring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups.Conclusions: Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.This study was funded by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341); Spanish Ministry of Education (Grant no. SB2010-0025); Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-01); Further support was received by Abbott Laboratories, Granada, Spain

Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils

It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio